Dental Pulp Stem Cell Conditioned Medium Enhance Osteoblastic Differentiation and Bone Regeneration.

Abstract

Background: Cell-free approaches, utilizing mesenchymal stem cell secretome, have promising prospects in various fields of regenerative medicine. In this study, we examined in vitro and in vivo the potential of dental pulp stem cell-conditioned medium (DPSC-CM) for bone regeneration.

Methods: The secretome of undifferentiated stem cells from dental pulp were collected, and the effects of this DPSC-CM were assessed for osteodifferentiation of osteoblast-like cells (MG-63) and osteoblasts deriving from DPSC. Cell proliferation, alkaline phosphatase (ALP) activity, gene expression of Runt-related transcription factor 2 (Runx2), Bone Sialoprotein (BSP), Osteocalcin (OCN), and extracellular matrix mineralization were evaluated. The rat caudal vertebrae critical size defect model was to investigate the effect of DPSC-CM in vivo.

Results: Results showed that DPSC-CM induced cell growth, and increased ALP activity and the expression of key marker genes at an early stage of osteoblastic differentiation compared to control. A rat bone defect model was used to illustrate the effect of DPSC-CM in vivo. The bone density within the defects were improved using conditioned medium, even though there was no significant difference between the control and DPSC-CM groups. The analysis of DPSC-CM by human growth factor antibody array revealed the presence of several factors involved in osteogenesis.

Conclusion: Taken together, these findings indicate that DPSC-CM is a promising therapeutic candidate for bone regenerative therapy, accelerating the maturation of osteoblastic cells. And even though safety and efficiency of DPSC-CM have to be confirmed in preclinical studies, these results represent a first step toward clinical application.